ProjectSummary/Abstract Thepurposeofthisprojectproposalistostudytheeffectsofexposuretogestationaldiabetesmellitus(GDM)in utero on hippocampal structure and function in children ages 7-10 years. Approximately 10% of children are exposedtogestationaldiabetesinutero,andGDMincidenceisontherise.InuteroexposuretoGDMhasbeen linkedtoanincreasedrisktowardsdevelopingmetabolicdisorders,suchasobesityandtype2diabetesduring adulthood, as well as cognitive deficits and neurobehavioral disorders in offspring. Animal studies show that youngratsexposedtoGDMinuterohaveimpairedhippocampalstructureandfunction,includingneuronalloss, altered cell signaling, and memory impairments. The hippocampus is a brain region involved in many broad functionsofmemoryandlearning,anditsdevelopmentisextremelysensitivetoinuteroinsults,includingaltered bloodglucoselevels.Thus,inuteroexposuretoGDMmaycauseabnormalitiesinthedevelopmentofthefetal programmingofthehippocampus,whichinturnleadstodeficienciesinmemoryprocessingintheoffspring.In linewiththishypothesis,arecentstudyshowedthatGDM-exposedchildren(ages7-9years)hadspecificdeficits on the working memory subscale of the Wechsler Intelligence Scale for children. Additionally, 12-month old infantswhowereexposedtoGDMinuteroexhibitedimpaireddeclarativememory,aswellasauditoryandvisual recognition memory when compared to unexposed age-matched controls. While memory was investigated in thesepriorstudies,hippocampalmemorywasnotspecificallyexplored.Basedonpriorstudies,wehypothesize thatinuteroexposuretomaternalgestationaldiabeteswillresultinreducedhippocampalgreymatter volumeandreducedhippocampalmemoryperformanceinchildrenaged7-10yearsoldwhencompared tounexposedchildrenmatchedforage,gender,ethnicityandmaternalpre-pregnancybodymassindex. Totestthishypothesis,wewillusestateoftheartmagneticresonanceimaging(MRI)methodologiestomeasure hippocampalgreymattervolumeandawell-validatedrelationalmemorytasktoassesshippocampal-dependent memory function in a unique cohort of well-characterized children who were exposed to GDM in utero and matchedunexposedchildren.